Halo dinitro-alkanoic acid esters of alkanediols

ABSTRACT

A PROCESS FOR CONTROLLING THE GROWTH OF BACTERIA AND FUNGUS COMPRISING TREATING THE BACTERIA OR FUNGUS WITH AN EFFECTIVE AMOUNT OF A COMPOUND OF THE FORMULA:   CL-C(-NO2)2-A2-COO-R2   WHEREIN A2 IS LOWER ALKYLENE AND R2 IS LOWER ALKYL.

United States Patent Ofice 3,732,289 Patented May 8, 1973 US. Cl.260-487 2 Claims ABSTRACT OF THE DISCLOSURE A process for controllingthe growth of bacteria and fungus comprising treating the bacteria orfungus with an effective amount of a compound of the formula:

wherein A is lower alkylene and R is lower alkyl.

This application is a division of copending application Ser. No.616,147, filed Jan. 3, 1967, which, in turn, is a divisional applicationof Ser. No. 326,286, filed Nov. 26, 1963, now Pat. No. 3,359,334.

This invention relates to certain novel halo dinitro com pounds andtheir method of preparation.

It is an object of this invention to prepare certain novel organiccompounds. It is another object of this invention to prepare new nitrocompounds in a novel manner. Still another object of this invention isto provide novel antibiotic and antifungal compositions. These and otherobjects of this invention will be apparent from the detailed descriptionwhich follows.

One type of the novel compounds of this invention has the followinggeneral formula:

Xian carbon atoms;

-A -CN wherein A is an alkylene radical preferably having from 1 toabout 20 carbon atoms;

wherein A, is an alkylene radical, preferably from 1 to 2O carbons; andR and R, are the same or different and are selected from the groupconsisting of hyrogen, hydrocarbyl, preferably alkyl or aryl having from1 to about 12 carbons, -hydroxyalkyl preferably having from 1 to about12 carbons;

wherein A are alkylene, preferably of from 1 to 10 carbons;

wherein A and R are alkylene, preferably of from 1 to 20 carbons;

wherein the Ar, groups are alkylene, preferably of from 1 to 20 carbons;and R is alkylene, preferably of from 1 to 20 carbons or vinylene(-CH=CH); n is an integer of from 1 to 2 and being equal to the valenceof R; and X is chloro or bromo.

Illustrative compounds within the scope of Formula I include:

5-chloro-5,5-dinitro-2-hydroxy pentane, 6-bromo-6,6-dinitro3-hydroxyhexane, 5-bromo-5,5-dinitro-1,Z-pentanediol,l-chloro-1,l-dinitro-Z-cyanoethane,

l-brorno- 1, l-dinitrovaleronitrile,N-butyl-3-chl0ro-3,3-dinitrop-ropionamide,N-decyl-S-chloro-5,5-dinitropentanamide,N-w-hydroxyethyll-dinitrobutyramide,N,N-diethyl-4-chloro-4,4-dinitrobutyramide,2-chloro-2,2-dinitroethyl-6-chloro-6,6-dinitrohexanoate,4-chloro-4,4-dinitrobutyl-4-chloro-4,4-dinitrobutyrate, 1,3 -bis-(4-chloro4,4-dinitrobutyry10xy) -propane, 1,10-bis-(4-chloro-4,4-dinitrobutyryloxy)-decane, 1, 8-bis- 3-chloro-3,3-dinitropropionyloxy) -octane, bis-(3-chloro-3,3-dinitropropyl)adipate, bis-(3-chloro-3,3-dinitropropyl) maleate,bis-(5-chloro-5,S-dinitropentyl) adipate,bis-(5-chloro-5,5-dinitropentyl) maleate,bis-(S-bromo-S,S-dinitropentyl) octanedioate,bis-(5-bromo-5,5-dinitropentyl) maleate, bis-(2-chloro-2,Z-dinitroethyl)dodecanedioate, bis-(2-chloro-2,2-dinitroethyl) maleate.

In general, the compounds of Formula I are prepared by reacting chlorineor bromine with the corresponding salt of an organic gem-dinitrocompound in accordance with the following general reaction:

wherein A, R, X and n are as defined above, and M is an alkali oralkaline earth metal such as sodium, potassium, lithium, or calcium.

Alternatively, certain of the compounds of Formula I may be prepared byprocedures other than that set forth in Equation II. These alternativereactions are hereinafter set forth.

When R in Formula I is the halo dinitro compounds of this invention areprepared according to the following reaction equation:

wherein X and A are as defined above and Z is lower alkyl, i.e., from 1to 6 carbons.

When R is in the above Formula I, the reaction is as follows:

wherein X, R and A are as defined above and Z is hydroxy, chloro orbromo.

WhenRis in Formula I, the reaction scheme is in accord with thefollowing:

wherein X, A and R are as defined above and Z is hydroxy, chloro orbromo.

The above reaction is conveniently carried out in any inert polar ornon-polar solvent in which the reactants are soluble, i.e., water,methanol, ethanol, benzene, chloroform, etc. The proportions of thereactants employed in the reaction are not critical. Normally,stoichiometrically equivalent amounts are used since this results in themost economical utilization of the reactants. The reaction temperatureshould normally be sufficiently high so that the reactants will dissolveto a substantial degree in the reaction medium, but in any event, thereaction temperature should be below the composition temperature of thereactant. Normally, the reaction is conducted at a temperature betweenabout 20 C. and about +120 C. The most preferred temperature is fromabout l0 C. to about C. Pressure is not critical in this reaction.Therefore, while any pressure can be used, the reaction is normally rununder atmospheric pressure. Agitation of the reactants such as bymechanical stirrer, while desirable in that it increases the reactionrate, is not necessary. The novel compounds of this invention may beisolated in conventional manner such as by extraction, distillationand/or filtration.

In the esterification reaction indicated above in Equations III to VI,it may be desirable in some cases in order to increase the reactionrate, to include in the reaction mixture a small, effective catalyticamount (0.1% to about 20% by weight based on total weight of reactants)of an acid esterification catalyst such as aluminum trichloride orpolyphosphoric acid.

To more clearly illustrate our invention the following examples arepresented. It is to be understood, however, that these examples areintended merely as an illustrative embodiment of the invention. In theexamples, the percentages are by weight unless otherwise indicated.

EXAMPLE I Preparation of bis-(2-chloro-2,2-dinitroethyl) maleate To asolution of 83 g. 2,2-dinitropropane-1,3-diol in 150 ml. methanol at 0C. was added, in portions, with shaking and hand-stirring, a coldsolution of 32.5 g. potassium 2,2-dinitroethanol precipitatedimmediately. After standing in ice for half an hour, it was filtered andwashed well with cold methanol. The wet filter-cake was suspended in 250ml. water, and, with good stirring, chlorine introduced at 0 C. to 5 C.After 40 minutes, all the salt had disappeared and an oil had separatedon the bottom of the flask. The mixture was light green; it was stirredfor 15 minutes longer, the oil separated and the aqueous phase extractedthree times with diethyl ether. The oil and ether solution were combinedand dried over sodium sulfate. Removal of the solvent under vacuum lefta very light green, slightly lachrymatory oil. Distillation at 0.4 to0.5 mm. and 57.5 C. to C. yielded 41 g. (0.24 mole) of2-chloro-2,3-dinitroethanol. The 2-chloro-2,2-dinitroethanol is thenreacted with 0.14 mole of maleic acid at 50 C. to 60 The bis-(2-chloro-2,2-dinitroethyl) maleate is obtained in good yields.

EXAMPLE II Preparation of methyl 4-chloro-4,4-dinitrobutyrate A 500 ml.round-bottom 3-neck flask was fitted with mechanical stirrer,thermometer, and dropping funnel. It was charged with 57.2 g. (0.258mole) crude methyl 5-hydroxy-4,4-dinitrophentanoate [Klager, Journal of01'- ganic Chemistry 16, 162-163 (1951)] in 150 ml. methanol. At 015 C.solution of 6.8 g. sodium (0.30 mole) in ml. methanol was added dropwiseover 30 minutes. Stirring was continued for an additional 45 minutes.The yellow sodium salt of methyl 4,4-dinitrobutyrate salt was collectedon a filter and washed with cold methanol. The wet salt was dissolved in200 ml. water to a total volume of 250 ml. Then 82 ml. of the aqueoussolution was charged to a 300 ml. round-bottom 3-neck flask fitted withstirrer, thermometer and gas inlet tube. At 5 C., chlorine wasintroduced with stirring. The temperature rose to 14 C. in 5 minutes,and a heavy yellow oil separated. Stirring was continued for 5 minutesafter the temperature began to fall, while a slow stream of chlorine wasintroduced. The oil was separated, and the aqueous phase was extractedonce with 1 ml., then with 40 ml. diethyl ether. The combined extractswere washed with 200 ml. water, and dried over sodium sulfate. Followingremoval of solvent by evaporation, the residue was submitted to vacuumdistillation. Two fractions were collected:

(I) -B. P. 60 to 66 at 0.15 mm. 1.0 g., 11 1.4614 (11) RP. 66 to 69 at0.15 mm., 7.1 g., 12 1.4615

Both were colorless liquids, and were combined.

Elemental analysis.--Calcd for C I-I N O Cl (percent): C, 26.58; H,3.12, Cl, 15.64. Found (percent): C, 26.52; H, 3.38; Cl, 16.75.

EXAMPLE III 2-bromo-2,2-dinitroethyl 4-bromo-4,4-dinitrobutyrate To 5.0g. of 4% oleum (prepared by adding 120 g.) of 30% fuming sulfuric acidto 100 g. of 96% sulfuric acid) was added 1.8 g. (0.0050 M)2-bromo-2,2-dinitroethanol and 1.36 g. (0.0050 M) methyl4-b-romo-4,4-dinitrobutyrate. Both substances dissolved readily with aslight rise in temperature. The solution was very light yellow. Afterthree days at room temperature, a few drops of the reaction mixture wasstirred with ice; no solid was obtained. The reaction mixture was keptin an oil-bath at 50 C. for 22 hours. No solid product was isolated withice. The temperature of the oil-bath was raised to 75 C. and maintainedthere for hours. The reaction mixture was poured on ice with stirring; anearly colorless, waxy solid separated. After thoroughly washing withwater, the solid was left to dry on a porous plate. The crude esterweight 0.50 g. (22% M.P. 66 to 72 C. Recrystallization from diisopropylether gave colorless product, M.P. 71.5 to 73 C.

Elemental analysis.Calcd for (percent): C, 15.87; H, 1.33; N, 12.34.Found (percent): C, 16.03; H, 1.32; N, 12.68.

When the above example was repeated using 2-chloro- 2,2-dinitroethanoland methyl 4-chloro-4,4-dinitrobutyrate (prepared according to ExampleII) in lieu of 2-bromo- 2,2-dinitroethanol and methyl4-bromo-4,4-dinitrobutyrate, respectively,2-chloro-2,2-dinitroethyl-4-chloro-4,4-dinitrobutyrate is obtained ingood yields.

EXAMPLE IV 4-bromo-4,4-dinitrobutyranilide Fifteen grams (0.058 M)4-bromo-4,4-dinitrobutyric acid and thirty milliliters (0.42 M) thionylchloride were refluxed for 45 minutes. The excess thionyl chloride wasremoved under vacuum, and the acid chloride recovered by distillation. Asolution of 5.83 g. (0.0212 M) of the 4-bromo-4,4-dinitrobutyrylchloride in 10 ml. benzene was added gradually, over 45 minutes, to asolution of 3.72 g. (0.040 M) aniline in 7 ml. benzene at reflux. Theprecipitate which formed when the aniline solution was added tended todissolve at the beginning, but complete solution was not attained. Themixture darkened as the reaction proceeded. The walls of the flask wererinsed with 5 to 10 ml. fresh benzene, and refluxing continued for 30minutes. After cooling, an attempt to extract the aniline hydrochloridewith water caused crystallization of the crude product in the separatoryfunnel. The anilide was dissolved with heating. The benzene solution,while still warm, was washed twice with water, boiled to remove waterazeotropically, and, after cooling, treated with an equal volume ofhexane. The crude product was filtered, washed with hexane, andair-dried. Wt. 4.8 g. (68%) M.P. 116 to 121 C. On standing, anadditional 0.3 g. (M.P. 90 to 126 C.) was collected from the motherliquor and wash. The crude, tan anilide (4.8 g.) was recrystallized from70 ml. isopropanol and ml. water, and decolorized twice with charcoal.The product was very light yellow; wt. 2.9 g. (corresponding to a 43%yield) M.P. 133 to 135 C. A small sample, recrystallized again fromaqueous isopropanol, was still light yellow and melted at 134 to 136 C.

Elemental analysis.Calcd for (percent): C, 36.16; H, 3.04; N, 12.65; Br,24.05. Found (percent): C, 36.75; H, 3.23; N, 12.46; Br, 24.34.

When the above example is repeated employing ethylamine in lieu ofaniline and 4-chloro-4,4-dinitrobutyric acid in place of4-brorno-4,4-dinitrobutyric acid, N-ethyl-4-chloric-4,4-dinitrobutyramide is obtained.

EXAMPLE V 1,4-bis- 4-bromo-4,4-dinitrobutyryloxy) -butane4-bromo-4,4-dinitrobutyryl chloride (5.22 g., 0.0203 M) was added to1,4-butanediol (0.79 g., 0.0088 M). The reaction mixture became hot, andhydrogen chloride was evolved. The clear viscous light yellow mixturewas placed in an oil-bath at 85 to 100 C. for minutes; it was taken upin about 10 ml. benzene, and the product precipitated by the gradualaddition of 30 ml. hexane. The colorless crystals were collected andwashed with hexane; wt. 4.0 g. (76%), M.P. 80 to 82 C. A small samplerecrystallized twice (for elemental analysis) from benzene-hexane meltedat 84 to 86 C. The main portion (3.6) was recrystallized once frombenzene-hexane (1:1); wt. 3.1 g. (86% recovery), M.P. 84 to 86 C.

Elemental analysis.Calcd for (percent): C, 25.37; H, 2.84; N, 9.86; Br,28.14. Found (percent): C, 26.15; H, 3.00; N, 9.59; Br, 28.38.

When the above example is repeated using 4-chloro- 4,4-dinitrobutyrylchloride in place of 4 bromo-4,4-dinitrobutyryl chloride and ethyleneglycol in lieu of 1,4-butanediol, a good yield ofbis-(4-chloro-4,4-dinitrobutyryloxy)- I ethane is obtained.

EXAMPLE VI Bis- (2-bromo-2,2-dinitroethyl) adipate2-bromo-2,2-dinitroethanol (5.5 g. 0.0255 M), adipyl chloride (2.2 g.,0.012 M), and 2 drops of concentrated sulfuric acid were heated on thesteam bath. Evolution of hydrogen chloride began almost immediately.After 45 minutes, the reaction mixture was poured into ice and water.The precipitated ester was broken up in a mortar and washed with water.The ester was then slurried on a funnel with one normal sodium carbonatesolution, filtered, and washed well with water. Five and one-half gramsof crude product (M.P. 70 to 74 C.) were obtained after air drying. Theester was purified by dissolving in 25 ml. benzene, charcoaling, andadding 35 ml. hexane to the hot filtrate. Crystallization took place at20 C. The adipate was filtered, washed with cold hexane, and dried;weight 4.5 g. (70%), M.P. 72 to 74 C. A small sample was againrecrystallized from benzene-hexane for elemental analysis (M.P. 74 to 76C.).

Calcd for: Br, 29.57%. Found: Br, 28.78%.

EXAMPLE VII Bis-(2-chloro-2,2-dinitroethyl) adipate2-chloro-2,Z-dinitroethanol (11 g., 0.065 M), adipyl chloride (5.5 g.,0.030 M), and 4 drops of concentrated sulfuric acid were heated on thesteam-bath for 30 minutes. Evolution of hydrogen chloride began even onmixing in the cold. The light yellow solution was poured into ice andwater. The light tan semi-solid which resulted after a few minutesstirring could not be broken up into small particles in a mortar. It waswashed successively with water, one normal sodium carbonate'solution,and again with water, as well as possible and left to dry on a porousplate. The crude ester (10 g., M.P. 32 to 40 C.) was recrystallized from35 ml. diisopropyl ether. The mixture was chilled at 20 C. and thecrystals collected, Washed with cold solvent, and dried; weight 6.0 g.,M.P. 38 to 48 C. A small sample was again recrystallized fromdiisopropyl ether (M.P. 49 to 51 C.) and submitted for elementalanalysis:

Calcd for: Cl, 15.73%. Found: Cl, 16.09%.

The main portion of the water was recrystallized a second time fromdiisopropyl ether (20 ml.), and 3.8 g. (28%) of the product, M.P. 47 to52 C., collected.

When the above example was repeated using sebacic acid in lieu of adipylchloride, bis-(2-chloro-2,2-dinitroethyl) sebacicate was obtained.

EXAMPLE VIII Preparation of l-(chloro-l,l-dinitrobutyronitrile To onemole of 1,l-dinitrobutyronitrile (prepared by the addition of one moleof dinitromethane to one mole of acrylonitrile) is added 1 M potassiumhydroxide at about 40 to 50 C. to form the potassium salt of 1,1-dinitrobutyronitrile. About 100 grams of the salt is then dissolved inabout 2 liters of water. Then 100 ml. of this aqueous solution ischarged to a 300 ml. round-bottom 3-neck flask fitted with stirrer,thermometer and gas inlet tube. At to 10 C., chlorine gas is introducedwith stirring. The addition of chlorine is continued for about 0.5 hour.The water is removed by evaporation under vacuum. The productl-chloro-1,l-dinitro-3-cyano propane is obtained in good yields. Whenthe foregoing example is repeated utilizing1,1-dinitro-3-methyl-butyronitrile in lieu of 1,1-butyronitrile,1-chloro-1,1-dinitro-3- methyl-butyronitrile is obtained.

EXAMPLE IX Preparation of chloro-5,5-dinitro-1,2-pentanediol To one moleof 5,5-dinitro-1,2-pentanediol (prepared by the addition of one mole ofhydrogen peroxide to one mole of 5,5,5-trinitro-1,Z-pentanediol) isadded 1 M potassium hydroxide at about 40 to 50 C. to form the potassiumsalt of 5,5-dinitro-1,2-pentanediol. About 100 grams of the salt is thendissolved in about 2 liters of water. Then 100 ml. of this aqueoussolution is charged to a 300 ml. round-bottom 3-neck flask fitted withstirrer, thermometer and gas inlet tube. At 0 to C., chlorine gas isintroduced with stirring. The addition of chlorine is continued forabout 0.5 hour. The water is removed by evaporation under vacuum. Theproduct 5-chloro-5,5-

dinitro-1,2-pentanediol is obtained in good yield.

When the foregoing example is repeated utilizing 5,5- dinitro-Z-pentanolin lieu of 5,5-dinitro-1,2-pentanediol, S-chloro-5,5-dinitro-2-pentanolis obtained.

In addition to the novel compounds within the scope of Formula I arestill another class of novel polynitro compounds. The compounds have thefollowing general formula:

wherein A is a lower alkylene group preferably having from 1 to about 6carbon atoms such as methylene, ethylene, butylene and hexamethylene; Ris a lower alkyl group preferably having from 1 to 8 carbons such asethoxy (-OC I-I methoxy (OCH etc.

Typical of the compounds within the scope of Formula VII are:2,2-dinitrobutyl formate, 3,3-dinitrooctyl formate, 5,5-dinitrohexylformate, ethyl-2,2-dinitropropy1 carbonate, hexyl-4,4-dinitrodecylcarbonate, isopropyl- 2,2-dinitropropyl carbons and propyl2,2-dinitropropy1 carbonate.

The novel esters of the above formula are prepared in accordance withthe following general reaction:

wherein A R and Y are as defined above; and Z is hydroxy or halogen,preferably chlorine or bromine.

The above reaction is conveniently, although not necessarily carried outin any inert solvent in which the reactants are soluble, i.e., benzene,toluene or hexane. The proportions of the reactants employed in thereaction are not critical. Normally, stoichiometrically equivalentamounts are used since this results in the most economical utilizationof the reactants. Thus, usually one mole of alcohol is used per mole ofacid or halo carbonate. The reaction temperature should normally besutficiently high so that the reactants will dissolve to a substantialdegree in the reaction medium, but in any event, the reactiontemperature should be below the composition temperature of the reactant.Normally, the reaction is conducted at a temperature between about 0 C.and about 100 C. The most preferred temperature is from about C. toabout C. Pressure is not critical in this reaction. Therefore, while anypressure can be used, the reactant is normally run under atmosphericpressure.

The above reaction is preferably conducted in the presence of aneffective catalytic amount of an acid esterification catalyst such asaluminium chloride or boron trifiuoride.

EXAMPLE X 2,2-dinitropropyl formate To a solution of 16.0 g. (0.10 M.,pure) 2,2- dinitropropanol in 22 ml. formic acid (98 to 100%) was addeda spatula-tip of anhydrous aluminum chloride. After refluxing for 23hours, the mixture was poured into icewater and the crude esterseparated with the aid of 30 ml. methylene chloride. The organic phasewas extracted first with 50 ml., and then with 25 ml. of cold one normalsodium hydroxide solution, washed twice with water, and dried overnight.Removal of the solvent in vacuo left 2.0 g. (11% of theory) of verylight green liquid, 11 1.4486. Distillation at 72.5 to 73.5 C./0.6 mm.gave a colorless distillate, 1.4487.

Elemental anaLvsis-Calcd for C H N O (percent): C, 26.97; H, 3.40; N,15.73. Found (percent): C, 27.33; H, 3.37; N, 15.60.

When the foregoing example is repeated substituting 3,3-dinitrobutanolfor 2,2-dinitropropanol, a good yield of 3,3-dinitrobutyl formate isobtained.

EXAMPLE XI Methyl 2,2-dinitropropyl carbonate 25 C. Mm. Grams n13 7 -7.8 1.4486 III 76 0. 4--0.5 1.2 1.4487 i The residue (0.7 g.) wasslightly viscous and light brown in color. The crude carbonate(Fractions I, II and III C. Mm Grams my I 88-93 0.6 1 6 1.4422 II 93-940.6 2 4 1.4425 III 94 6 0 1 Fraction II showed no presence of hydroxylin the infrared spectrum.

Elemental analysis (I'I). Calcd for C H N O (per cent): C, 28.85; H,3.87; N, 13.46. Found (percent): C, 29.49; H, 4.37; N, 13.92.

When the above example is repeated using 3,3-dinitrol-pentanol in lieuof 2,2-dinitropropanol, and ethyl bromoformate in place of methylchloroformate, a substantial quantity of essentially pure ethyl3,3-dinitropropyl carbonate is obtained.

The compounds of this invention, which contain a plurality of nitrogroups, are inherently useful as high explosives. These compounds canalso be used in any conventional explosive missile, projectile, rocketor the like, as the main explosive charge. An example of such a missileis described in US. Pat. 2,470,162, issued May 17, 1949. One way ofusing such high explosives in a device such as that disclosed in US.Pat. 2,470,162 is to absorb the liquid explosive in an absorbentmaterial such as cellulose, wood pulp, or sawdust. The resultantdynamite-type explosive can then be packed into the warhead of themissile. A charge thus prepared is sufficiently insensitive to withstandthe shock entailed in the ejection of a shell from a gun barrel or arocket launching tube under the pressure developed from ignition of apropellant charge, and can be caused to explode on operation of animpact or time-fuse mechanism firing a detonating explosive such as leadazide or mercury fulminate.

Certain of the novel compounds of this invention are also useful asfungicides, in the prevention of bacterial growth, and as plasticizersfor solid rocket propellant formulations.

This example describes a particular method of preparing a novelpropellant composition from the following ingredients employing methyl2,2-dinitropropyl carbonate as a plasticizer:

EXAMPLE XII The aluminum powder is stirred into about /3 of the requiredvolume of polypropylene glycol and glycerol monoricinoleate. The mixtureis prepared in a stainless steel container, using a copper-berylliumspatula. Mixing is continued for about 10 minutes.

The aluminum slurry is added to a conventional mixer equipped withfacilities for heating, cooling and vacuumizing the propellant mix. Thewalls of the aluminum slurry container are scraped thoroughly. Thecontainer is rinsed with /2 of the required volume of dioctyl azelateand the rinses are added to the mixer. The remaining polypropyleneglycol is added to the mixer. The methyl 2,2-dinitropropyl carbonate ismixed with the remaining dioctyl azelate until homogeneous and thesolution is then added to the mixer.

With the mixer off, the ferric acetylacetonate, phenylbetanaphthylamine, and lecithin are added through a 40- mesh screen. Thecopper chromite is added to the mixer.

The mixer is covered and mixed by remote control for 15 minutes under 26to 28 inches of vacuum, after which it is stopped and the vacuumreleased with dry nitrogen. The cover is removed from the mixer and theoxidizer is added by remote control with the mixer blades in motion.

After all of the oxidizer has been added, the mixer is stopped andscraped down. The propellant mass is mixed for 15 minutes at F. under 26inches vacuum by remote control. The mixer is stopped and the vacuumreleased with dry nitrogen. The tolylene diisocyanate is added, afterwhich the mass is mixed for 10 minutes at 70 F. and 26 inches of vacuumby remote control. The vacuum is then released with dry nitrogen and themixture is cast.

Propellants prepared in the foregoing manner have a specific impulse inthe range from 225 to about 250 seconds.

The compounds of Formula I are especially useful as antibiotics and asanti-fungals. In this respect, the compounds of Formula I wherein X ischloro are far superior in effectiveness to the corresponding bromocompounds. Most preferred of the compounds within the scope of Formula Iare those of the formula:

wherein A is lower alkylene and R is lower alkyl.

The compounds of Formula VII are highly effective as anti-fungals. Alsouseful as anti-fungals in accordance with the procedures of thisinvention are the ether compounds having the general formula:

(X) No:

Other classes of compounds which can be used as antifungals according toour invention are:

(XI) N02 H H N01 R1n?A1nOC-CH=CHC OA 0-( ]-R wherein both A groups arelower alkylene from 1 to about 6 carbons, and the R groups are alkyl offrom 2 to 6 carbons;

(XII) /o-0g2 /NO3 O-Ca N02 (XIII) wherein both R groups are lower alkyl,preferably of from 1 to 6 carbons; and

wherein R in each instance is lower alkyl of from 1 to about 6 carbons.

The compounds of Formula XI, and their method of preparation aredisclosed in assignees copending US. application Ser. No. 326,287, filedNov. 26, 1963.

The compounds of Formula XII, and their method of preparation aredisclosed in assignees copending US. application Ser. No. 326,285, filedNov. 26, 1963.

The compounds of Formulae XIII and XIV, and their method of preparationare disclosed in assignees copending US. application Ser. No. 326,288,filed Nov. 26, 1963, now Pat. No. 3,306,929.

In the anti-bacterial test a compound within the scope of Formula I wascompared in vitro to penicillin against B. subtillis (gram positivebacteria) and to chloromycetin against E. coli (gram negative bacteria).The compound tested was the compound of Example II, methyl 4-chloro-4,4-dinitrobutyrate.

EXAMPLE XIII Two glass plates were uniformly and completely coated witha sterile aqueous solution of gum agar pH 5.7. The agar film wasinoculated with the B. subtillis. Upon each plate was then placed asmall 0.10 ml. glass cylinder, one filled with a standard solution ofpenicillin containing 0.001 mg. per milliliter, on the other plate anaqueous solution of the methyl-4-chloro-4,4-dinitrobutyrate containingone mg. per milliliter. The plates were then incubated by maintainingthem at a temperature of about 37 C. After about 15 hours a clear zoneof growth inhibition around each of the cylinders could be observed. Thearea of the zone of growth inhibition around the cylinder containingmethyl 4-chloro-4,4dinitrobutyrate was somewhat greater than the area ofthe zone of growth inhibition around the cylinder containing thestandard penicillin solution.

EXAMPLE XIV Two glass plates were uniformly and completely coated with asterile aqueous solution of gum agar. The agar film was inoculated withthe E. coli. Upon each plate was then placed a small glass cylinder, onefilled with a standard solution of penicillin containing one unit permilliliter, on the other plate an aqueous solution of themethyl-4-chloro-4,4-dinitrobutyrate. The plates were then incubated at atemperature of about 37 C. After about 15 hours a clear zone of growthinhibition around each of the cylinders could be observed. The area ofthe zone of growth inhibition around the cylinder containingmethyl-4-chloro-4,4-dinitrobutyrate was somewhat greater than the areaof the zone of growth inhibition around the cylinder containing thestandard penicillin solution.

Anti-fungal tests were conducted using compounds 12 within the scope ofFormulae IX to XIV. In each of these tests the test organism wastrichophyton metagrophytes.

EXAMPLE XV SCALE 0Inactive l-Poor, (less active than undecylenic acid)2Good, (approximately equal to undecylenic acid) 3 Excellent, (at least2.5 times more effective than undecylenic acid) The results obtained inaccordance with the abovedescribed anti-fungal tests are set forth inthe following table.

TABLE I Compound: Rating Methyl 4-chloro-4,4-dinitrobutyrate (Compoundof Formula I) 3 2,2-dinitropr0pyl formate (Compound of Formula VII) 3Bis-(2,2-dinitrobutyl) maleate (Compound of Formula XI) 3 Methyl2,2-dinitropropyl carbonate (Compound of Formula VII) 3 Cyclic sulfateof 2,2-dinitro-1,3 propanediol (Compound of Formula XII) 3 Cyclic phenylphosphite of 2,2-dinitro-1,3-propanediol (Compound of Formula XIl) 32,2-dinitropropyl-2,2,3,3-tetrafiuoro propyl ether (Compound of FormulaIX) 3 5,5,5-trinitro 1,2-pentanediol diacetate (Compound of Formula XIV)3 2,2-dimethyl 4(3,3,3'-trinitropropyl) 1,3-dioxolane (Compound ofFormula XIII) 3 Bis-(2,2-dinitropropyl maleate 2Bis-(2,-bromo-2,2-dinitroethyl) adipate 2 Application of theantibacterial and antifungal compounds of this invention for the variouspurposes disclosed may be made from solutions in suitable solventcarriers, such as alcohol, benzene, and petroleum naphtha, or fromdispersion in aqueous or other media, or in the form of a dust. They maybe used in combination with supplementary agents, such as talc,bentanite, tricalcium phosphate, various clays, spreading agents,stickers and other adjuvants commonly used in bacterial and funguscontrol compositions. They may also be used in combination with otherbacteria and fungus control agents, such as sulfur fungicides or organicfungicides and various other agents commonly used in fungicidal andinsecticidal applications. When the bactericides and fungicides of thisinvention are used in conjunction with adjuvants, the active ingredientsis employed in a bactericidally or fungicidally effective amount,normally from about 0.01% to by weight of the total composition. Cautionshould be used in using these products since many of them are irritantto the skin.

It will be understood that various modifications may be made in thisinvention without departing from the spirit thereof or the scope of theappended claims.

We claim:

1. The compounds having the general formula:

14 wherein A and R are alkylene of 1 to 20 carbon atoms, OTHERREFERENCES and X is selected from the group consisting of chloro ChemAbstracts, ,Vol. 53: Mayflyune ,1959 00L 1104, and bromo- Glicksmon eta1.

2. The compound 1,4-b1s-(4-bromo-4,4-d1n1trobutyryl- Y)' 5 LORRAINE A.WEINBERGER, Primary Examiner References Cited UNITED STATES PATENTS3,387,044 6/1968 Grakauskas 260-487 3,396,187 8/1968 Benziger et a1.260485 H 1 260-4045 3,356,174 12/1967 Karnlet 260487 J. F. TERAPANE,Assistant Examiner

